1. Field of the Invention
The present invention generally relates to inhalation devices such as metered dose inhalers (MDIs), nebulizers, and dry powder inhalers. More particularly, the invention is directed to a dose or timing controlled actuator that operates in conjunction with an inhalation device to prevent both patient under-compliance with prescribed medication dosing and patient abuse of or dependence on prescribed medication. Specifically, the invention contemplates the use of an actuator to prevent patient actuation of the inhalation device at non-prescribed intervals or at higher than prescribed doses, and the use of an alarm to notify the patient regarding undercompliance/underdosing situations and attempted abuse situations.
2. Description of the Prior Art
Patient compliance with a doctor's instructions on prescribed medication is extremely important in the treatment of medical disorders. Although the rate of patient compliance is higher when he or she must return to the hospital or physician's office to receive the medication, most drug treatment regimens require the patient to administer the drugs at regular intervals without supervision by hospital personnel or the patient's physician or other qualified medical personnel. Obviously, the treatment of a medical disorder will be frustrated if the patient does not administer the drugs as prescribed. In the past, physicians have had to rely on the patient's self-interest in his or her own well being to assure that drugs are properly administered as scheduled.
With anti-anxiety or sedative/hypnotics, such as valium and barbiturates, it is widely recognized that there is a real possibility that the patient will abuse or become dependent on the drug. In Clinical Toxicology 8(5):495-513 (1975), it was argued that physicians should avoid the prescription of barbiturates because of the risk of dependence and the high toxicity of the drugs. Miller et al., American Family Physician v40, n4, p175(9) (October 1989), reported on the use of benzodiazepine drugs in the treatment of anxiety and particularly discussed the identification of dependence and addiction to these drugs. Bird, Northwest Medicine 69(8)533 (1970), reported on the problem of sedative overdose and suggested that sedatives should only be dispensed in small quantities and only on a restricted basis. Magnes, Applied Therapeutics (Toronto) 7:649 (1965) discussed the problems in the use of tranquilizing drugs in treating patients with psychoneuroses and demonstrated that in many patients treated with ethclorvynol an addiction develops.
Many drugs have a narrow therapeutic range and can have severe side effects. It is well recognized that controlling the dosing of these types of drugs is important in mitigating problems with side effects. Salzman, Hospital and Community Psychiatry (Washington) 33:2, 133-136 February 1982, reported that elderly patients are more susceptible to psychotropic drug toxicity, severe extrapyramidal side-effects from neuroleptics, and anticholinergic side-effects from tricyclic antidepressants. Milner, Medical Journal of Australia (Sydney) 2(3):153-155 (1969), reported that psychotropic drugs can have gastrointestinal side effects. Miller et al., American Family Physician v40, n4, p175(9) (October 1989), reported that benzodiazapine drugs pose adverse side effects to patients.
Many drugs can be extremely expensive (e.g., certain purified peptides and proteins). Controlling patient dosing of these drugs can have economic benefits.
An MDI typically comprises a canister under pressure fitted with a metering valve where the canister is filled with an aerosol formulation that includes a drug dissolved or dispersed in a propellant together with a surfactant. Nebulizers are devices which include mechanical or electronic devices (e.g., piezoelectric element) to atomize a drug suspension positioned in a containment cup. Nebulizers include an air or other gas source to deliver the atomized drug to the patient as a fine mist. Dry powder inhalers include mechanical or electronic devices to produce a fine mist from a powdered drug composition. MDIs, nebulizers, and dry powder inhalers have been used for many years to treat pulmonary disorders such as asthma. Examples of the types of drugs which have been routinely provided by these aerosolizing devices include: .beta.-agonists such as albuterol (salbutamol), isoproterenol, ephedrine, epinephrine, salmeterol, terbutaline; corticosteroids such as triamcinolone acetonide, beclomethasone diproprionate, dexamethasone, and aldosterone; allergic mediators such as cromclyn sodium; antibiotics; and anticholinergics.
Patient non-compliance with inhalation devices has been recognized as a major medical problem. In 1985, Dr. Spector reported in Spector, "Is your Asthmatic Patient Really Complying?", Annals of Allergy, 55:552-556 (1985), that patient compliance using a nebulizer to deliver lodoxamide, a cromolyn-like aerosol having a prophylactic (as opposed to immediate) bronchodilator effect, was extremely poor. In the investigation, patients were provided with a device called a Nebulizer Chronolog which contained a microswitch and timer that recorded the time of each use of the nebulizer. In addition, the patients were asked to record their use of the nebulizer in a diary. The patients were not told that the time of actuation of the nebulizer was also being automatically recorded. Over a several week study where lodaxamide was to be delivered at prescribed hourly intervals, it was determined from the automatically recorded usage data that all patients underdosed themselves. The mean rate of underusage was 48% for the study and the highest rate of underusage was 95.6%. Nevertheless, many patients did not tell the truth about their underusage in their diaries.
In a later study, Mawhinney et al., "Compliance in clinical trials of two nonbronchodilator, antiasthma medications", Annals of Allergy, 66:294-299 (1991), two groups of patients were provided with MDIs that were insertable into Nebulizer Chronolog devices (reported to be available from the ATA Corporation of Denver, Colo.). One group received either lodoxamide or placebo, while the other group received tixocortol pivalate or placebo. Even though patients were told they were being monitored, compliance was very low. Underusage was observed in a number of patients. In addition, overusage was observed in a number of patients, especially on days preceding follow up visits to the physicians office. In fact, only one patient in thirty four was found to be truly compliant.
There is a need to improve patient compliance with prescribed dosing schedules. As was reported in Nedelmann, Nervenarzt 53(1):33-38 (1982), it was reported that patient compliance with a doctor's drug prescription for psychotherapeutic drugs is only around 50%. Furthermore, Kahl et al., Public Health Reports Vol. v107, issue n1, page p37(110) (January-February 1992) reported that overuse, underuse and inappropriate use of drugs by elderly patients are common problems. Several different solutions have been proposed for helping improve patient compliance. For example, Morris et al., Comprehensive Psychiatry 15(6):537-547 (1974), suggested that overdoses with the widely prescribed psychotherapeutic drugs may be avoided if there was a requirement of including an emetic or some other agent as a deterrent in the drugs, Witt, Dissertation Abstracts International 39(11):5321-B (1979) discusses the use of post-discharge pill count measurements, Beardsley, (Ph.D Dissertation University of Minn. 1977) reports a study that demonstrated increased compliance with a patient's increased knowledge about drugs gained by close interaction with pharmacists, and Venulet, Journal of Clinical Pharmacology and Biopharmacy (Munchen) 15(4):151-154 (1977), notes that having doctors understand the personality and sociocultural background of patients will aid in compliance. This invention is particularly directed to an improved inhalation device which aids in assuring patient compliance.
There is also a need for an inhalation device which can provide some assurance that a patient is not circumventing a dosing schedule by not inhaling medication. Mawhinney et al., Annals of Allergy, 66:294-299 (1991), points out that the Nebulizer Chronolog has no mechanism to determine whether a patient has activated the MDI without inhaling medication or how often they might have done so. Mawhinney et al. particularly note that Fox, Bull Int. Union Against Tuberculosis 32:307-331 (1961), reports that the self-administration of medicaments was studied in depth and it was particularly noted that home health visitors frequently found supplies of unused medications in a patient's home, despite finding a correct number of pills in the containers presented to the health investigators. Hence, there is a tendency of some patient's to "cheat" on dosing schedules. Preventing a patient's ability to "cheat" would help ensure compliance with prescribed dosing schedules.